Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells

Jonathan A. Cohn, Theresa V. Strong, Marina R. Picciotto, Angus C. Nairn, Francis S. Collins, J. Gregory Fitz

Research output: Contribution to journalArticle

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Abstract

Background: Liver dysfunction is a common manifestation of cystic fibrosis (CF), a disease caused by mutations affecting the CF transmembrane conductance regulator (CFTR). The aim of this study was to examine the distribution and role of CFTR in liver. Methods: CFTR messenger RNA was detected in cryosections of human liver by in situ hybridization. CFTR immunoreactivity was detected using antibodies raised against two CFTR peptides. Results: The predominant site of CFTR messenger RNA and immunoreactivity in liver is the intrahepatic bile duct. CFTR is not detected in hepatocytes of normal liver or in livers exhibiting bile duct proliferation. Within bile duct cells, CFTR is localized at or near the apical plasma membrane. Conclusions: The apical localization of CFTR in bile duct cells suggests a model explaining how the CFTR-associated Cl- channel contributes to normal biliary secretion. This model suggests that if CFTR expression could be promoted in intrahepatic duct cells by somatic gene therapy, this might prevent the occurrence of liver disease in CF.

Original languageEnglish (US)
Pages (from-to)1857-1864
Number of pages8
JournalGastroenterology
Volume105
Issue number6
StatePublished - 1993

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Cystic Fibrosis Transmembrane Conductance Regulator
Bile Ducts
Epithelial Cells
Liver
Cystic Fibrosis
Liver Diseases
Intrahepatic Bile Ducts
Messenger RNA
Genetic Therapy
In Situ Hybridization
Hepatocytes
Cell Membrane
Peptides
Mutation
Antibodies

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Cohn, J. A., Strong, T. V., Picciotto, M. R., Nairn, A. C., Collins, F. S., & Fitz, J. G. (1993). Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. Gastroenterology, 105(6), 1857-1864.

Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. / Cohn, Jonathan A.; Strong, Theresa V.; Picciotto, Marina R.; Nairn, Angus C.; Collins, Francis S.; Fitz, J. Gregory.

In: Gastroenterology, Vol. 105, No. 6, 1993, p. 1857-1864.

Research output: Contribution to journalArticle

Cohn, JA, Strong, TV, Picciotto, MR, Nairn, AC, Collins, FS & Fitz, JG 1993, 'Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells', Gastroenterology, vol. 105, no. 6, pp. 1857-1864.
Cohn, Jonathan A. ; Strong, Theresa V. ; Picciotto, Marina R. ; Nairn, Angus C. ; Collins, Francis S. ; Fitz, J. Gregory. / Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. In: Gastroenterology. 1993 ; Vol. 105, No. 6. pp. 1857-1864.
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AB - Background: Liver dysfunction is a common manifestation of cystic fibrosis (CF), a disease caused by mutations affecting the CF transmembrane conductance regulator (CFTR). The aim of this study was to examine the distribution and role of CFTR in liver. Methods: CFTR messenger RNA was detected in cryosections of human liver by in situ hybridization. CFTR immunoreactivity was detected using antibodies raised against two CFTR peptides. Results: The predominant site of CFTR messenger RNA and immunoreactivity in liver is the intrahepatic bile duct. CFTR is not detected in hepatocytes of normal liver or in livers exhibiting bile duct proliferation. Within bile duct cells, CFTR is localized at or near the apical plasma membrane. Conclusions: The apical localization of CFTR in bile duct cells suggests a model explaining how the CFTR-associated Cl- channel contributes to normal biliary secretion. This model suggests that if CFTR expression could be promoted in intrahepatic duct cells by somatic gene therapy, this might prevent the occurrence of liver disease in CF.

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